long term problems using c/l - Parkinson's Movement

Parkinson's Movement
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long term problems using c/l

tandolino
tandolino

I am really concerned abote the long term use of C/L. I would rather deal with the termors and stiffness being under medicated than to have major problems associated with side effects of C/L. Accoding to this link below carbidopa has bad long term side effects and can be replaced with less harmful items. i was diagnosed 3 years ago. comments please, I am new here

theparkinsonsplan.com/blog/...

43 Replies
oldestnewest

That has been refuted here:

healthunlocked.com/parkinso...

and some additional info here:

healthunlocked.com/parkinso...

While I am extremely grateful for this experience and insight, I don't think that exactly counts as "refuted" in my mind. How do we know that doses of carbidopa and vitamin B6 (separated by a couple of hours) still aren't interacting? From my understanding, it's not just that they might interact in the digestive system, but that they would interact in the blood or other tissues.

jeffreyn cites this below:

journeywithparkinsons.com/2...b-vitamins-folate-b6-b12-reduce-homocysteine-levels-produced-by-carbidopalevodopa-therapy

"And further inspection of the possible reaction properties between vitamin B6, carbidopa and even levodopa suggests that vitamin B6 could be forming a Schiff Base, which would totally compromise the ability of either compound to function biologically (this is illustrated below)."

It seems dangerous to not get enough vitamin B6, but taking too much is a problem, too. Offsetting doses seems to have worked for you, but it feels like an imperfect solution. Presumably, it is working to treat your symptoms. But have you been tested for your vitamin B6 levels?

That to me is the pertinent question: is it possible to maintain B6 levels at an adequate amount for broad enzyme function?

If I go on to levodopa medication, I will either take mucuna pruriens and avoid carbidopa altogether, or else take C/L and offset with vitamin B6.

[A further comment on word usage. Assuming that time-offset B6 supplements do work: Saying that a problem has a solution doesn't mean that the problem has been "refuted", it means the problem has been addressed.]

However, I just found this out. If a person takes L-dopa without a decarboxylase inhibitor such as carbidopa, but still takes a vitamin B6 supplement (say 10 mg), then it is possible that taking vitamin B supplements will reduce the efficacy of L-dopa medication.

ncbi.nlm.nih.gov/pmc/articl...

Apparently, the added B6 "increas[es] the activity of the enzyme dopa decarboxylase outside the central nervous system." More L-dopa is converted to dopamine outside the CNS, and thus can't make it through the blood brain barrier to the target.

It's complicated.

Grumpy77
Grumpy77 in reply to ElliotGreen

If i may ask - whats Akinetic PD and what are the symptoms? thank you

ElliotGreen
ElliotGreen in reply to Grumpy77

Bradykinesia means slow movement. Akinesia means lack of movement. Hypokinesia means low movement. I think they are all related.

I would probably say that hypokinesia is the most accurate wording, but akinesia is more common in terms of describing a Parkinson's disease subtype.

Speaking for myself, my ability to move my right hand and my right arm are reduced. That is my primary symptom of PD. It affects my writing, my typing, my day-to-day living, and my ability to do qigong forms. I also no longer ride a bicycle because of it. It also gives me a bit of a limp on my right side.

Grumpy77
Grumpy77 in reply to ElliotGreen

Thats similar to my symptoms except that in addition i have tremors- that is growing in frequency and amplitude weekly (it seems).

So you don't have tremors do you? or did you manage to suppress tremors with medications?

ElliotGreen
ElliotGreen in reply to Grumpy77

In general, I only have slight tremors. Sometimes when I am stressed out, they get worse. I am currently taking various supplements, but not any medication. My tremors aren't so bad as to warrant medication, the akinesia might be, but I haven't taken that step yet.

chartist
chartist in reply to Grumpy77

Grumpy77,

I remember that you were/are a regular user of HDT/B-1. You are describing a worsening of your symptoms and Dr. Costantini has always maintained that a worsening of symptoms after months of HDT use would likely mean that your dose may now be a bit too high. I have heard several members who have used HDT for many months describe a worsening of symptoms and a minor dose reduction was able to ameliorate them.

In Kia17's case, the dose required to affect a positive change was to merely not take HDT on one day of the week. That is a very fine dosage adjustment when you actually figure it out on a per day basis, but that is all it took to put Kia back on track.

Dr. Costantini did not know the exact reason for this, but he saw it often enough to recognize it and have a pretty good idea of just how little of an adjustment it would take to correct the problem.

Art

Grumpy77
Grumpy77 in reply to chartist

You are correct in that the worsening of my symptoms has to do with dosage. But its probably due to dose reduction rather than too high dosage. Because the worsening of my symptoms coincided with when I had to reduce the dosage (and the brand) because I decided to get my GP to prescribe Thaimine B1 to me, which he did. But the brand was different and the regularity of the prescribed B1 arrival could not keep up with 3g i used to take per day so i was forced to reduce to 2g per day sometimes less. The prescribed B1 is 100mg, so i have to gulp down 20 tablets or less p/d, so i'm going back to 3g p/d

I thought effectiveness of HDT should be independent of brand, what do you think?

chartist
chartist in reply to Grumpy77

Grumpy77,

I agree that the brand should not matter. What should be in the pill or capsule should be exactly as stated on the label! Unfortunately, independent labs have determined that this is not always the case, so it is useful to stick with brands that other members have found effective such as the Vitacost 500 mg capsules. On the positive side, over the past ten years or so, manufacturers seem to be trying harder to put in their products what is stated on the label.

Getting back to what you knew as a good and effective dose for you makes plenty of sense to me.

Art

Indeed there will still be some interaction, but that is okay. Some B6 will become inactivated by the carbidopa, but as long as one has an abundance of B6 there is plenty of B6 left over and available as needed. We can make sure we have an abundance by taking more B6 than carbidopa. At the second link I addressed the issue of B6 toxicity - that is avoided by taking the active rather than the inactive form of B6. As long as we take the proper form of B6 there is no toxicity issue and no known limitation on dosage.

The other concern is whether B6 in circulation substantially inactivates carbidopa in the digestive tract. My experience is that it does not.

Marty Hinz and company contend that the only solution is the Hinz protocol - giving up carbidopa entirely. For example see a comment by an M.D. supporting the Hinz protocol at the first link above. I believe I have refuted that contention.

See also my reply to jeffreyn regarding the Frank Church article.

👍

EDIT: See my other comments where I discuss this issue at more length. Carbidopa gets distributed throughout the body except for the Central Nervous System. That means it will interact with B6 throughout the body, and not just the gastrointestinal tract. Furthermore, it is said to interact with enzymes that use vitamin B6. Some scientific articles say that carbidopa irreversibly binds to these enzymes. I've tried to contact the authors of these papers but I've not heard back.

To me, the issue remains an open question, and the efficacy of offsetting carbidopa by dosing with b6 is uncertain. I think the practice seems advisable, but I'm not certain that it makes the problem of b6 enzyme depression go away.

rebtar
rebtar in reply to park_bear

Do we know what amount of carbidopa deactivates what amount of b6? Do we know this is 1:1 in mg?

park_bear
park_bear in reply to rebtar

A molecule of P5P(B6) weighs about 9% more than a molecule of carbidopa.

Actual molecular weights: 247.142 vs 226.229 respectively

They were close enough that I chose not to add this complication. Congratulations for having an awareness of this issue!

rebtar
rebtar in reply to park_bear

Thanks, Parkbear. So taking about an equivalent amount should do the trick.

How old are you?

Lots of different opinions on this matter. If this article is correct, perhaps supplementing withB6 would solve the problem.

I’ve been taking it for 15 years. No side effects.

LAJ12345
LAJ12345 in reply to Baileytwo

Which? L dopa or b6?

Baileytwo
Baileytwo in reply to LAJ12345

25/100 during the day 50/200 at night

TL500
TL500 in reply to Baileytwo

one of each per day? Thanks

The article linked to by tandolino states:

"... because Carbidopa irreversibly binds to vitamin B6, the vitamin necessary for the conversion of L-Dopa to Dopamine, over time, the added drug inadvertently causes lower levels of Dopamine in the brain ..."

Putting aside the issue of whether this statement is completely correct, I find it interesting that the article does not address the most-obvious question in the reader's mind. That is, why can't you just take a B6 supplement to compensate for B6 that has been "disabled"?

In fact, you can, as park_bear explains in his comment (see first reply, above).

As also explained, if you are not careful, and take B6 at the wrong time (or take too much of it), you could disable too much carbidopa, which would result in too little levodopa reaching the brain. Just such a scenario (too much B6) was described by Prof. Frank Church in a Sept. 2017 blog post.

journeywithparkinsons.com/2...

At the linked webpage (about half way down the page, just before the picture of the 4 supplement labels) the section is titled: "Beware of taking a huge excess of vitamin B6 in the presence of carbidopa/levodopa, a cautionary tale".

park_bear
park_bear in reply to jeffreyn

Regarding the cautionary tale - he had been taking B6 and carbidopa/ levodopa at the same time. Moreover, as is typical, is B complex contained the cheap inactive form of B6 which has been toxic for some users at the hundred milligram dose he was using.

His ensuing analysis is also incorrect because he uses a one compartment model which does not accurately represent the situation of having carbidopa in the G.I. tract and B6 in general circulation

Okay, but carbidopa doesn't just operate in the G.I. tract. It goes in the general circulation, too. It just doesn't make it through the blood brain barrier.

I took a look and was unable to find any reference that apportions the activity of carbidopa between the G.I. tract and peripheral tissues. All I can say is my personal experience of separating the B6 and the carbidopa in time seems to leave the activity of carbidopa / levodopa unimpaired.

Roger that.

There is some information regarding absorption, and carbidopa's operation in the periphery at this link.

drugbank.ca/drugs/DB00190

"The action of carbidopa is focused on peripheral DDC as this drug cannot cross the blood-brain barrier."

They mis-cite a paper on absorption. They say 58% bioavailability for carbidopa, but that is a comparison of slow-release versus regular Sinemet. Nevertheless, that [and another] resource make it clear that both levodopa and carbidopa are absorbed into the body, but carbidopa doesn't cross the BBB.

ncbi.nlm.nih.gov/pubmed/268...

ncbi.nlm.nih.gov/pubmed/109...

Cjbro2000
Cjbro2000 in reply to park_bear

@park_bear Which do you take first: the B6 or the carbidopa? Or does it matter as long as I wait 2 hours between?

park_bear
park_bear in reply to Cjbro2000

Does not matter as long as it is two hours between. Even better if something is eaten within that period.

Would replacing Carbidopa-Levodopa by Benserazide-Levodopa avoid the problem and give about same benefit?

ElliotGreen
ElliotGreen in reply to Parkie-

You might want to check, but I think the same thing happens with Benserazide.

I would just give sinimet a try and see how it works for you. Most people do well on it and you could try Park Bears timing advice on B6 if you are concerned about that. Your link is a sales pitch for an expensive alternative that is less than forthcoming with the actualities.

Carbidopa activity is not limited to the gastrointestinal tract. It is also absorbed and does get into "general circulation", and this activity is significant. (However, it does not cross the blood brain barrier.) For example, see the citation:

ncbi.nlm.nih.gov/pubmed/109...

also:

"Carbidopa is distributed widely in body tissues except the CNS [central nervous system]."

glowm.com/resources/glowm/c...

I am not taking carbidopa/levodopa medication yet, but should I start, I would attempt park_bear's advice for offset dosing between C/L and B6.

However, I would be sure to have my B6 tested to make sure I wasn't too deficient.

I also don't think that park_bear fully counters this claim in the Hinz paper:

"Carbidopa and the active metabolite of benserazide, trihydroxybenzylhydrazine, irreversibly bind to and permanently deactivate PLP and PLP-dependent enzymes.18,19,70–74."

Note that it is not only affecting PLP (the active form of B6), but also enzymes and proteins bound to PLP.

So there isn't a "safe refuge" for vitamin B6 or its dependent enzymes. Temporally offset B6 supplementation may help counteract the effects of carbidopa on this wide array of enzymes, but it's going to be a balancing act.

What I’m not entirely clear on is whether carbidopa just “steals” a B6 from the enzyme, or if it permanently shuts down the whole PLP-enzyme assemblage. Perhaps Hinz may have overstated it somewhat in stating that PLP -dependent enzymes are “permanently deactivated”. It may just be that the PLP is stolen and permanently deactivated, but another molecule of B6/PLP could get the enzyme rolling again. But I don't know. Maybe the whole assemblage is shut down. [I have actually sent an email to some Italian researchers who may be able to shed light on this question.]

I am looking at this article:

journals.plos.org/plosone/a...

At any rate, the picture is somewhat worse (or uncertain) than park_bear was suggesting.

A 2016 review:

ingentaconnect.com/content/...

Parkinson’s Disease: Recent Updates in the Identification of Human Dopa Decarboxylase Inhibitors

"CarbiDOPA and benserazide are the inhibitors currently used in Parkinson's disease treatment. However, carbiDOPA and trihydroxybenzylhydrazine, the active metabolite of benserazide, are substrate analogues both endowed with a hydrazine function, which irreversibly bind not only to DDC but also to free pyridoxal 5’-phosphate and pyridoxal 5’-phosphate-dependent enzymes. Therefore, the lack of DOPA decarboxylase specificity, responsible for various side effects and adverse reactions, is a negative factor in such treatment of the disease."

It sure looks like they're saying that carbidopa binds the whole B6 enzyme, Not just the B6 part of it. This doesn't look good.

PEB69
PEB69 in reply to ElliotGreen

Hi, I have the same concerns about sinemet. It's the wording 'irreversible binding' to the enzyme that concerns me, is it irreversible during the life of the enzyme, are replacement enzymes made periodically, or are there a finite number of the b6 enzymes and once we've damaged them with carbidopa that's it. If someone comes off their sinemet, will over time new enzymes be produced and this is why they 'feel better'. It will be interesting to see what the Italian researches say about it.

ElliotGreen
ElliotGreen in reply to PEB69

The body can synthesize new enzymes, yes.

Enzymes are proteins. They are macromolecules. There's a whole factory process where the DNA for a protein is transcribed into RNA, and then RNA is decoded and used to assemble a protein, and then the protein is folded into its proper shape. It takes time, energy, and biochemical resources. The body also needs to somehow detect that these specific proteins are deficient, and to signal to make more.

*If* what these articles are saying is true, and whole enzyme macromolecules are being basically "booted" (like those things that parking attendants use to incapacitate a car), but PERMANENTLY, then I see that as a big deal. Yes, your body can make more, but then some of those are going to get booted the next time you take carbidopa.

C/L since diagnosis.......19 years ....... progression increases....... C/L increases and agonists.........DBS.........removed agonists and decreased C/L ............. things are not perfect but it had been so much worse prior to DBS. I'm on 25/100 C/L Sinimet 3 pills every 3 hours including when my dyskinesias (and my prostate that needs it own zip code) wake me like clockwork. I'd hate to be without C/L and haven't attributed anything negative to how long Ive taken it.

Jlloy5
Jlloy5 in reply to Pelley

I'm considering removing the agonists (Neupro patch) as well after DBS in October. Did you wait until recovery or just stop taking it from surgery. I know that I should "wean" off of it. I'm terrified of being awake for the DBS. Did you do the rechargeable battery or did you do the ones that need to be replaced?

I am not going to throw any more research at you, but will share my experience. I am 46 years old and have been living with Parkinson's for 12 years. C/L works really well, but as the disease progressed, I found myself having to take more and more of it. I keep up with a busy life, still with 3 children in the house, 1 who is still in grade school. I am currently scheduled for DBS. The side effects of the c/l, in my experience, are crippling, and far worse than my Parkinson's symptoms. I literally cancel my plans every couple of weeks, and stay in bed to "detox" from it. I suffer from levadopa induced dystonia and severe, on the floor, thrashing, dyskinesia from the c/l. I have used Mucuna Pruriens, but only recently, and it works very well, but I have not figured out how to squeeze in a meal without it failing. Other than that, it works better and longer than the c/l. I also experienced dyskinesia with the Mucuna Pruriens. I have learned that it is more common in younger individuals to experience dyskinesia from c/l. After DBS, I plan to fight hard to never take those "angry yellow pills" again. Maybe I'll win, maybe I'll lose, but my life has been very challenging dealing with the results of taking c/l. Better safe than sorry in my opinion.

Kecher
Kecher in reply to Jlloy5

Jlloy5......What kind of Mucuna Pruriens do you use? (Capsules, powder, brand name) Also, what dosages? How quickly does it "kick" in? Thank you for sharing.

Jlloy5
Jlloy5 in reply to Kecher

I use Barlowe's capsules. I'm trying to attach a link but it isn't letting me.

I either take one with a half c/l 25/100 or I take 2. Either way I'll get around 4 hours of relief vs 1 hour. I use the c/l with it if I'm going to eat soon, because it works better.

I don't take any pills either , eventually I might have to.

It is progressing , and the lack of pills makes me look for solutions elsewhere (exercise,

food , hand therapy and whatever helps) . It is hard and a full time job to take these medicines. Thanks everybody for all the information provided.

Good sources of vitamin B6

Vitamin B6 is found in a wide variety of foods, including:

pork

poultry, such as chicken or turkey

fish

bread

wholegrain cereals, such as oatmeal, wheatgerm and brown rice

eggs

vegetables

soya beans

peanuts

milk

potatoes

some fortified breakfast cereals

Very interesting thread. I was diagnosed with Parkinson's almost 15 years ago at the age of 38 and still on active duty in the USAF. initially my symptoms were very mild, and I was prescribed Mirapex. It did a good job of controlling my symptoms, but it also gave me severe edema in my lower legs. After about 6 years my symptoms had progressed to the point that i needed more medicine, or so I thought. I started taking c/l w/entecapone, and Selegilne. I never questioned the doctor. After about 7 years of that regime I began to question the long term outlook for taking all these pills, which were clearly less and less effective as time went by.. Which brings us to the present. Three weeks ago i started taking Rytary. Just more c/l. But I am also aggressively pursuing any/all natural therapies. Since the beginning of 2019 i have tried manitol, B1/HDT, KETO diet, medical marijuana, CBD oil, Macuna,,B12, copious amounts of exercise, and anything else that sounds safe and shows promise. I would much prefer to ingest plants, herbs, and anything else that grows in nature as opposed to something made by a chemist in a lab,

I have never seen a study that shows the downside of 40+ years of c/l medicine, which is what I'm looking at if I live to be 80.,

There's got to be a better way!!

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